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Introduction Over the past two decades, the incidence of acute rheumatic fever (ARF) and chronic rheumatic heart disease (RHD) have dramatically declined in wealthier regions of the world as a result of preventative programmes, improved living standards and access to cardiac surgery. Nevertheless, ARF and RHD are still public health problems in less-developed regions of the world such as Oceania, south Asia and sub-Saharan Africa. Aim We report on clinical, therapeutic and prognostic aspects as well as the difficulties encountered during this first series of surgery for rheumatic valve disease in Mali. Methods This was a prospective, descriptive study conducted at the Andre Festoc Cardiac Surgery Centre from September 2018 to August 2019. Results The frequency of patients having been operated on for rheumatic valve disease was 44.73% (68 patients). The mean age of the patients was 18 ± 10 years with extremes of five and 60 years. The gender ratio was 0.7. The delay to treatment was between one and three years for 39.7% of the patients. The main diagnoses found were: mitral regurgitation in 50% of patients, mitral stenosis in 16.2% and aortic regurgitation in 10.3%. Pulmonary artery systolic pressure was 35-50 mmHg in 19.1% of patients and more than 50 mmHg in 25%. The median cardiopulmonary bypass time was 132 minutes (60-276) and median extubation time was three hours (0-96). The main complications were cardiac, renal, neurological, respiratory, gastrointestinal and infectious. In the immediate postoperative period, we recorded three deaths, which is a mortality rate of 4.4%. Conclusions Humanitarian efforts have led non-governmental organisations (NGOs) to launch surgical programmes in low-and middle-income countries in an attempt to fill the gap in these fragile healthcare systems. Cardiac surgery requires much expertise from the medical staff, as well as many material and financial resources. Empowerment of the local team is a challenge that is being realised since taking these essential steps of companionship with the NGO la Chaine de l'Espoir.

Background The African Surgical OutcomeS-2 (ASOS-2) trial tested an enhanced postoperative surveillance intervention to reduce postoperative mortality in Africa. We undertook a concurrent evaluation to understand the process of intervention delivery. Methods Mixed-methods process evaluation, including field notes, interviews, and post-trial questionnaire responses. Qualitative analysis used the framework method with subsequent creation of comparative case studies, grouping hospitals by intervention fidelity. A post-trial questionnaire was developed using initial qualitative analyses. Categorical variables were summarised as count (%) and continuous variables as median (inter-quartile range [IQR]). Odds ratios (OR) were used to rank influences by impact on fidelity. Results The dataset included eight in-depth case studies, and 96 questionnaire responses (response rate 67%) plus intervention fidelity data for each trial site. Overall, 57% (n=55/96) of hospitals achieved intervention delivery using an inclusive definition of fidelity. Delivery of the ASOS-2 interventions and data collection presented a significant burden to the investigators, outstripping limited resources. The influences most associated with fidelity were: surgical staff enthusiasm for the trial (OR=3.0; 95% confidence interval [CI], 1.3–7.0); nursing management support of the trial (OR=2.6; 95% CI, 1.1–6.5); performance of a dummy run (OR=2.6; 95% CI, 1.1–6.1); nursing colleagues seeing the value of the intervention(s) (OR=2.1; 95% CI, 0.9–5.7); and site investigators' belief in the effectiveness of the intervention (OR=3.2; 95% CI, 1.2–9.4). Conclusions ASOS-2 has proved that coordinated interventional research across Africa is possible, but delivering the ASOS-2 interventions was a major challenge for many investigators. Future improvement science efforts must include better planning for intervention delivery, additional support to investigators, and promotion of strong inter-professional teamwork. Clinical trial registration ClinicalTrials gov NCT03853824.

Summary Background Risk of mortality following surgery in patients across Africa is twice as high as the global average. Most of these deaths occur on hospital wards after the surgery itself. We aimed to assess whether enhanced postoperative surveillance of adult surgical patients at high risk of postoperative morbidity or mortality in Africa could reduce 30-day in-hospital mortality. Methods We did a two-arm, open-label, cluster-randomised trial of hospitals (clusters) across Africa. Hospitals were eligible if they provided surgery with an overnight postoperative admission. Hospitals were randomly assigned through minimisation in recruitment blocks (1:1) to provide patients with either a package of enhanced postoperative surveillance interventions (admitting the patient to higher care ward, increasing the frequency of postoperative nursing observations, assigning the patient to a bed in view of the nursing station, allowing family members to stay in the ward, and placing a postoperative surveillance guide at the bedside) for those at high risk (ie, with African Surgical Outcomes Study Surgical Risk Calculator scores ≥10) and usual care for those at low risk (intervention group), or for all patients to receive usual postoperative care (control group). Health-care providers and participants were not masked, but data assessors were. The primary outcome was 30-day in-hospital mortality of patients at low and high risk, measured at the participant level. All analyses were done as allocated (by cluster) in all patients with available data. This trial is registered with ClinicalTrials.gov , NCT03853824 . Findings Between May 3, 2019, and July 27, 2020, 594 eligible hospitals indicated a desire to participate across 33 African countries; 332 (56%) were able to recruit participants and were included in analyses. We allocated 160 hospitals (13 275 patients) to provide enhanced postoperative surveillance and 172 hospitals (15 617 patients) to provide standard care. The mean age of participants was 37·1 years (SD 15·5) and 20 039 (69·4%) of 28 892 patients were women. 30-day in-hospital mortality occurred in 169 (1·3%) of 12 970 patients with mortality data in the intervention group and in 193 (1·3%) of 15 242 patients with mortality data in the control group (relative risk 0·96, 95% CI 0·69–1·33; p=0·79). 45 (0·2%) of 22 031 patients at low risk and 309 (5·6%) of 5500 patients at high risk died. No harms associated with either intervention were reported. Interpretation This intervention package did not decrease 30-day in-hospital mortality among surgical patients in Africa at high risk of postoperative morbidity or mortality. Further research is needed to develop interventions that prevent death from surgical complications in resource-limited hospitals across Africa. Funding Bill & Melinda Gates Foundation and the World Federation of Societies of Anaesthesiologists. Translations For the Arabic, French and Portuguese translations of the abstract see Supplementary Materials section.

During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.).

Summary Background Maternal influenza immunisation can reduce morbidity and mortality associated with influenza infection in pregnant women and young infants. We aimed to determine the vaccine efficacy of maternal influenza immunisation against maternal and infant PCR-confirmed influenza, duration of protection, and the effect of gestational age at vaccination on vaccine efficacy, birth outcomes, and infant growth up to 6 months of age. Methods We did a pooled analysis of three randomised controlled trials done in Nepal (2011–2014), Mali (2011–2014), and South Africa (2011–2013). Pregnant women, gestational age 17–34 weeks in Nepal, 28 weeks or more in Mali, and 20–36 weeks in South Africa, were enrolled. Women were randomly assigned 1:1 to a study group, in which they received trivalent inactivated influenza vaccine (IIV) in all three trials, or a control group, in which they received saline placebo in Nepal and South Africa or quadrivalent meningococcal conjugate vaccine in Mali. Enrolment at all sites was complete by April 24, 2013. Infants and women were assessed for respiratory illness, and samples from those that met the case definition were tested for influenza by PCR testing. Growth measurements, including length and weight, were obtained at birth at all sites, at 24 weeks in South Africa, and at 6 months in Nepal and Mali. The three trials are registered with ClinicalTrials.gov , numbers NCT01430689 , NCT01034254 , and NCT02465190 . Findings 10 002 women and 9800 liveborn infants were included. Pooled efficacy of maternal vaccination to prevent infant PCR-confirmed influenza up to 6 months of age was 35% (95% CI 19 to 47). The pooled estimate was 56% (28 to 73) within the first 2 months of life, 39% (11 to 58) between 2 and 4 months, and 19% (–9 to 40) between 4 and 6 months. In women, from enrolment during pregnancy to the end of follow-up at 6 months postpartum, the vaccine was 50% (95% CI 32–63) efficacious against PCR-confirmed influenza. Efficacy was 42% (12 to 61) during pregnancy and 60% (36 to 75) postpartum. In women vaccinated before 29 weeks gestational age, the estimated efficacy was 30% (–2 to 52), and in women vaccinated at or after 29 weeks, efficacy was 71% (50 to 83). Efficacy was similar in infants born to mothers vaccinated before or after 29 weeks gestation (34% [95% CI 12 to 51] vs 35% [11 to 52]). There was no overall association between maternal vaccination and low birthweight, stillbirth, preterm birth, and small for gestational age. At 6 months of age, the intervention and control groups were similar in terms of underweight (weight-for-age), stunted (length-for-age), and wasted (weight-for-length). Median centile change from birth to 6 months of age was similar between the intervention and the control groups for both weight and length. Interpretation The assessment of efficacy for women vaccinated before 29 weeks gestational age might have been underpowered, because the point estimate suggests that there might be efficacy despite wide CIs. Estimates of efficacy against PCR-confirmed influenza and safety in terms of adverse birth outcomes should be incorporated into any further consideration of maternal influenza immunisation recommendations. Funding Bill & Melinda Gates Foundation.

The tenth outbreak of Ebola virus disease (EVD) in North Kivu, the Democratic Republic of the Congo (DRC), was declared 8 days after the end of the ninth EVD outbreak, in the Equateur Province on August 1, 2018. With a total of 3,461 confirmed and probable cases, the North Kivu outbreak was the second largest outbreak after that in West Africa in 2014–2016, and the largest observed in the DRC. This outbreak was difficult to control because of multiple challenges, including armed conflict, population displacement, movement of contacts, community mistrust, and high population density. It took more than 21 months to control the outbreak, with critical innovations and systems put into place. We describe systems that were put into place during the EVD response in the DRC that can be leveraged for the response to the current COVID-19 global pandemic.

At the end of the 2013-2016 Ebola virus disease outbreak in Guinea, we implemented an alert system for early detection of Ebola resurgence among survivors. Survivors were asked to report health alerts in their household and provide body fluid specimens for laboratory testing. During April-September 2016, a total of 1,075 (88%) of 1,215 survivors participated in the system; follow up occurred at a median of 16 months after discharge (interquartile range 14-18 months). Of these, 784 acted as focal points and reported 1,136 alerts (including 4 deaths among survivors). A total of 372 (91%) of 408 eligible survivors had >1 semen specimen tested; of 817 semen specimens, 5 samples from 4 survivors were positive up to 512 days after discharge. No lochia (0/7) or breast milk (0/69) specimens tested positive. Our findings underscore the importance of long-term monitoring of survivors' semen samples in an Ebola-affected country.

Background In cattle, genome-wide association studies (GWAS) have largely focused on European or Asian breeds, using genotyping arrays that were primarily designed for European cattle. Because there is growing interest in performing GWAS in African breeds, we have assessed the performance of 23 commercial bovine genotyping arrays for capturing the diversity across African breeds and performing imputation. We used 409 whole-genome sequences (WGS) spanning global cattle breeds, and a real cohort of 2481 individuals (including African breeds) that were genotyped with the Illumina high-density (HD) array and the GeneSeek bovine 50 k array. Results We found that commercially available arrays were not effective in capturing variants that segregate among African indicine animals. Only 6% of these variants in high linkage disequilibrium (LD) (r2 > 0.8) were on the best performing arrays, which contrasts with the 17% and 25% in African and European taurine cattle, respectively. However, imputation from available HD arrays can successfully capture most variants (accuracies up to 0.93), mainly when using a global, not continent-specific, reference panel, which partially reflects the unusually high levels of admixture on the continent. When considering functional variants, the GGPF250 array performed best for tagging WGS variants and imputation. Finally, we show that imputation from low-density arrays can perform almost as well as HD arrays, if a two-stage imputation approach is adopted, i.e. first imputing to HD and then to WGS, which can potentially reduce the costs of GWAS. Conclusions Our results show that the choice of an array should be based on a balance between the objective of the study and the breed/population considered, with the HD and BOS1 arrays being the best choice for both taurine and indicine breeds when performing GWAS, and the GGPF250 being preferable for fine-mapping studies. Moreover, our results suggest that there is no advantage to using the indicus-specific arrays for indicus breeds, regardless of the objective. Finally, we show that using a reference panel that better represents global bovine diversity improves imputation accuracy, particularly for non-European taurine populations.

Summary Background Women across the world are mistreated during childbirth. We aimed to develop and implement evidence-informed, validated tools to measure mistreatment during childbirth, and report results from a cross-sectional study in four low-income and middle-income countries. Methods We prospectively recruited women aged at least 15 years in twelve health facilities (three per country) in Ghana, Guinea, Myanmar, and Nigeria between Sept 19, 2016, and Jan 18, 2018. Continuous observations of labour and childbirth were done from admission up to 2 h post partum. Surveys were administered by interviewers in the community to women up to 8 weeks post partum. Labour observations were not done in Myanmar. Data were collected on sociodemographics, obstetric history, and experiences of mistreatment. Findings 2016 labour observations and 2672 surveys were done. 838 (41·6%) of 2016 observed women and 945 (35·4%) of 2672 surveyed women experienced physical or verbal abuse, or stigma or discrimination. Physical and verbal abuse peaked 30 min before birth until 15 min after birth (observation). Many women did not consent for episiotomy (observation: 190 [75·1%] of 253; survey: 295 [56·1%] of 526) or caesarean section (observation: 35 [13·4%] of 261; survey: 52 [10·8%] of 483), despite receiving these procedures. 133 (5·0%) of 2672 women or their babies were detained in the facility because they were unable to pay the bill (survey). Younger age (15–19 years) and lack of education were the primary determinants of mistreatment (survey). For example, younger women with no education (odds ratio [OR] 3·6, 95% CI 1·6–8·0) and younger women with some education (OR 1·6, 1·1–2·3) were more likely to experience verbal abuse, compared with older women (≥30 years), adjusting for marital status and parity. Interpretation More than a third of women experienced mistreatment and were particularly vulnerable around the time of birth. Women who were younger and less educated were most at risk, suggesting inequalities in how women are treated during childbirth. Understanding drivers and structural dimensions of mistreatment, including gender and social inequalities, is essential to ensure that interventions adequately account for the broader context. Funding United States Agency for International Development and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO.

Summary Background A record number of people survived Ebola virus infection in the 2013–16 outbreak in west Africa, and the number of survivors has increased after subsequent outbreaks. A range of post-Ebola sequelae have been reported in survivors, but little is known about subsequent mortality. We aimed to investigate subsequent mortality among people discharged from Ebola treatment units. Methods From Dec 8, 2015, Surveillance Active en ceinture, the Guinean national survivors' monitoring programme, attempted to contact and follow-up all survivors of Ebola virus disease who were discharged from Ebola treatment units. Survivors were followed up until Sept 30, 2016, and deaths up to this timepoint were recorded. Verbal autopsies were done to gain information about survivors of Ebola virus disease who subsequently died from their closest family members. We calculated the age-standardised mortality ratio compared with the general Guinean population, and assessed risk factors for mortality using survival analysis and a Cox proportional hazards regression model. Findings Of the 1270 survivors of Ebola virus disease who were discharged from Ebola treatment units in Guinea, information was retrieved for 1130 (89%). Compared with the general Guinean population, survivors of Ebola virus disease had a more than five-times increased risk of mortality up to Dec 31, 2015 (age-standardised mortality ratio 5·2 [95% CI 4·0–6·8]), a mean of 1 year of follow-up after discharge. Thereafter (ie, from Jan 1–Sept 30, 2016), mortality did not differ between survivors of Ebola virus disease and the general population. (0·6 [95% CI 0·2–1·4]). Overall, 59 deaths were reported, and the cause of death was tentatively attributed to renal failure in 37 cases, mostly on the basis of reported anuria. Longer stays (ie, equal to or longer than the median stay) in Ebola treatment units were associated with an increased risk of late death compared with shorter stays (adjusted hazard ratio 2·62 [95% CI 1·43–4·79]). Interpretation Mortality was high in people who recovered from Ebola virus disease and were discharged from Ebola treatment units in Guinea. The finding that survivors who were hospitalised for longer during primary infection had an increased risk of death, could help to guide current and future survivors' programmes and in the prioritisation of funds in resource-constrained settings. The role of renal failure in late deaths after recovery from Ebola virus disease should be investigated. Funding WHO, International Medical Corps, and the Guinean Red Cross.

Understanding risk factors for Ebola transmission is key for effective prediction and design of interventions. We used data on 860 cases in 129 chains of transmission from the latter half of the 2013–2016 Ebola epidemic in Guinea. Using negative binomial regression, we determined characteristics associated with the number of secondary cases resulting from each infected individual. We found that attending an Ebola treatment unit was associated with a 38% decrease in secondary cases (incidence rate ratio (IRR) = 0.62, 95% confidence interval (CI): 0.38, 0.99) among individuals that did not survive. Unsafe burial was associated with a higher number of secondary cases (IRR = 1.82, 95% CI: 1.10, 3.02). The average number of secondary cases was higher for the first generation of a transmission chain (mean = 1.77) compared with subsequent generations (mean = 0.70). Children were least likely to transmit (IRR = 0.35, 95% CI: 0.21, 0.57) compared with adults, whereas older adults were associated with higher numbers of secondary cases. Men were less likely to transmit than women (IRR = 0.71, 95% CI: 0.55, 0.93). This detailed surveillance data set provided an invaluable insight into transmission routes and risks. Our analysis highlights the key role that age, receiving treatment, and safe burial played in the spread of EVD.

Clinical development of Ebola virus vaccines (EVV) was accelerated by the West African Ebola virus epidemic which remains the deadliest in history. To compare and rank the EVV according to their immunogenicity and safety. A total of 21 randomized controlled trial, evaluating seven different vaccines with different doses, and 5,275 participants were analyzed. The rVSVΔG-ZEBOV-GP (2 × 10 (7)) vaccine was more immunogenic (P-score 0.80). For pain, rVSVΔG-ZEBOV-GP (≤10 (5)) had few events (P-score 0.90). For fatigue and headache, the DNA-EBOV (≤ 4 mg) was the best one with P-scores of 0.94 and 0.87, respectively. For myalgia, the ChAd3 (10 (10)) had a lower risk (P-score 0.94). For fever, the Ad5.ZEBOV (≤ 8 × 10 (10)) was the best one (P-score 0.80). The best vaccine to be used to stop future outbreak of Ebola is the rVSVDG-ZEBOV-GP vaccine at dose of 2 × 10(7) PFU.

Introduction:drug-resistant tuberculosis is a major global health problem and a threat to health security given the increase in the number of cases and the challenges associated with care. Besides, the relationship between poor nutritional status and tuberculosis is clearly established. For relevant and evidence-based public health decision-making regarding the management of malnutrition in patients with drug-resistant tuberculosis in the initial phase, it is essential to estimate the prevalence of malnutrition and understand the risk factors associated with it. Methods:we performed a retrospective cohort study in drug-resistant tuberculosis patients aged 18 years and older, among which the nutritional status was assessed through BMI. All predictors were included in a prediction model using the multivariate logistic model according to the lowest Akaike criterion. Discrimination and model calibration was evaluated using receiver performance analysis, and the Hosmer and Lemeshow test. Results:this study revealed a prevalence of malnutrition of 64.7% in drug-resistant tuberculosis patients in our 218-patient series. The factors associated with malnutrition were: unsuccessful treatment, the active presence of mycobacterium tuberculosis, increased bacteriological conversion time, increased serum creatinine, increased transaminase SGPT of the liver, and anaemia. Some of the factors not associated with malnutrition included the history of anti-tuberculosis treatment, vomiting, hepatic SGPT, initial AFB count, smear and culture conversion time, depression, and chest x-ray. Conclusion:malnutrition remains a concern among drug-resistant tuberculosis patients in Guinea as it affects more than half of them with a negative impact on the outcome of treatment. Implementing specific interventions for these high-risk patients, including nutritional supplementation, psychosocial support, and treatment for tuberculosis, can improve management for better treatment outcomes.

The 10th and largest Ebola virus disease epidemic in the Democratic Republic of the Congo (DRC) was declared in North Kivu Province in August 2018 and ended in June 2020. We describe and evaluate an Early Warning, Alert and Response System (EWARS) implemented in the Beni health zone of DRC during August 5, 2018-June 30, 2020. During this period, 194,768 alerts were received, of which 30,728 (15.8%) were validated as suspected cases. From these, 801 confirmed and 3 probable cases were detected. EWARS showed an overall good performance: sensitivity and specificity >80%, nearly all (97%) of alerts investigated within 2 hours of notification, and good demographic representativeness. The average cost of the system was US $438/case detected and US $1.8/alert received. The system was stable, despite occasional disruptions caused by political insecurity. Our results demonstrate that EWARS was a cost-effective component of the Ebola surveillance strategy in this setting.

BackgroundEvidence has shown the benefits of labour companions during childbirth. Few studies have documented the relationship between the absence of labour companions and mistreatment of women during childbirth in low-income and middle-income countries using a standardised tool.MethodsWe conducted a secondary analysis of the WHO multi-country study on how women are treated during childbirth, where a cross-sectional community survey was conducted with women up to 8 weeks after childbirth in Ghana, Guinea, Nigeria and Myanmar. Descriptive analysis and multivariable logistic regression were used to examine whether labour companionship was associated with various types of mistreatment.ResultsOf 2672 women, about half (50.4%) reported the presence of a labour companion. Approximately half (49.6%) of these women reported that the timing of support was during labour and after childbirth and most of the labour companions (47.0%) were their family members. Across Ghana, Guinea and Nigeria, women without a labour companion were more likely to report physical abuse, non-consented medical procedures and poor communication compared with women with a labour companion. However, there were country-level variations. In Guinea, the absence of labour companionship was associated with any physical abuse, verbal abuse, or stigma or discrimination (adjusted OR (AOR) 3.6, 1.9–6.9) and non-consented vaginal examinations (AOR 3.2, 1.6–6.4). In Ghana, it was associated with non-consented vaginal examinations (AOR 2.3, 1.7–3.1) and poor communication (AOR 2.0, 1.3–3.2). In Nigeria, it was associated with longer wait times (AOR 0.6, 0.3–0.9).ConclusionLabour companionship is associated with lower levels of some forms of mistreatment that women experience during childbirth, depending on the setting. Further work is needed to ascertain how best to implement context-specific labour companionship to ensure benefits while maintaining women’s choices and autonomy.

Background Despite the predictive role of body weight variation in treatment outcome in multidrug-resistant tuberculosis (MDR-TB), few corroborating data are available. We studied weight variation in patients with MDR-TB to identify groups of weight change and to determine factors that influence these changes. Methods We analyzed patients with rifampicin resistance who were treated with an MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 at three major drug-resistant TB centers in Guinea. Patients were seen monthly until the end of treatment. Clinical outcome was the body mass index (BMI). We used a linear mixed model to analyze trajectories of BMI and a latent class mixed model to identify groups of BMI trajectories. Results Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3–8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m2. Factors associated with faster BMI progression were success of MDR-TB treatment (0.24 [SE 0.09] per kg/m2; p = 0.0205) and absence of lung cavities on X-ray (0.18 [0.06] per kg/m2; p = 0.0068). Two groups of BMI change were identified: rapid BMI increase (n = 121; 85%) and slow BMI increase (n = 22; 15%). Patients in the slow BMI increase group were mostly female (68%) had no history of TB treatment (41%), had a positive HIV infection (59%), and had a more severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelet count, and higher SGOT. These patients also had a longer time to initial culture conversion (log-rank test: p = 0.0218). Conclusion Quantitative BMI data on patients with MDR-TB treated with a short regimen allowed the identification of subgroups of patients with different trajectories of BMI and emphasized the usefulness of BMI as a biomarker for the monitoring of MDR-TB treatment outcome.

The 2014–2016 Ebola virus (EBOV) disease outbreak affected over 29000 people and left behind the biggest cohort (over 17000 individuals) of Ebola survivors in history. Although the persistence of EBOV in body fluids of survivors was reported before the recent outbreak, new evidence revealed that the virus can be detected up to 18 months in the semen, which represents the biggest risk of Ebola resurgence in affected communities. In this study, we review the knowledge on the Ebola flare-ups that occurred after the peak of the 2014–2016 Ebola epidemic in West Africa.

Background: The prevalence of non-tuberculous mycobacteria (NTM) has been increasing worldwide in both developed and developing countries. NTM infection is clinically indistinguishable from tuberculosis and therefore poses significant challenges in patient management, especially in patients chronically treated for pulmonary TB. In this study, we evaluated a new highly sensitive Multiplex MTB/NTM assay that can differentiate M. tuberculosis complex (MTBC) from all NTM, including the treatable and most common NTM, M. avium complex (MAC). Methods: We developed and optimized a new open- Multiplex MTB/NTM assay with two gene-targets for MTBC (IS6110/senX3-regX3) and two targets for MAC (IS1311/DT1) with samples spiked with stored strains and testing 20 replicates. Patients with presumptive TB and NTM were enrolled at the Pneumology Department of The University Teaching Hospital of Point G, in Mali. Finding: In the development stage, the new assay showed a high analytic performance with 100% detections of MTBC and MAC at only 5 colony forming units (CFUs). Overall, without the treatment failure cases, the Multiplex assay and the Xpert showed a sensitivity and specificity of 83·3% [66·4-92·6] and 96·6% [88·6-99·0], and 96·7% [83·3-99·4] and 80% [55·5-82·3], respectively. The Multiplex assay successfully detected all (5/5) the MAC cases. Interpretation: Our new Multiplex assay demonstrates better specificity than Xpert for all group studies, in addition to detecting potential NTM cases. The assay could therefore complement the widely used Xpert assay and enhance discrimination of TB and NTM infections. Funding Statement: This work was supported by the National Institutes of Health (R03AI137674, U54EB027049, D43TW010350 and UM1AI069471). Declaration of Interests: There are no conflicts of interest. Ethics Approval Statement: The study was approved by the Ethics Committee of the Faculty of Medicine, Pharmacy and Odonto-stomatology of the University of Sciences, Technics and Technologies of Bamako (USTTB) and the Institutional Review Board of Northwestern University.

Background By the end of the 2013–2016 West African Ebola Virus Disease (EVD) outbreaks, a total of 3814 cases (probable and confirmed) and 2544 deaths were reported in Guinea. Clearly, surveillance activities aiming at stopping human-to-human transmission have been the breakthrough of EVD outbreak management, but their application has been at times easier said than done. This article presents five confirmed or probable EVD cases that arose in Conakry towards the end of the Guinea epidemic, which demonstrate flaws in surveillance and follow-up. Case presentation For case 1, safe burial requirements were not followed. For cases 1 and 2, negative Polymerase Chain Reaction (PCR) results were interpreted as no infection. For the first case, the sample may have not been taken properly while for the second the disease was possibly at its early stage. Case 3 was stopped at a border health checkpoint and despite her high temperature she was allowed to continue the bus journey. For case 4, an oral swab sample was supposedly taken after death but could not be found for retrospective testing. Despite characteristic symptomatology, case 5 was not identified as a suspect case for as long as 3 weeks. Conclusion In epidemic contexts, health systems must be able to track all samples of suspect cases and deaths, regardless of their laboratory results. Social mobilization in communities and training in health care facilities must be strengthened at the tail of an outbreak, to avoid the natural slackening of disease surveillance, in particular for long-lasting and deadly epidemics.

The ongoing Ebola outbreak in the eastern Democratic Republic of the Congo is facing unprecedented levels of insecurity and violence. We evaluate the likely impact in terms of added transmissibility and cases of major security incidents in the Butembo coordination hub. We also show that despite this additional burden, an adapted response strategy involving enlarged ring vaccination around clusters of cases and enhanced community engagement managed to bring this main hotspot under control.

Background The ninth outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of the Congo occurred in Équateur Province from 8 May-24 July 2018. A system of health facility (HF)-based active case finding (ACF) was implemented in Mbandaka, a regional capital with four confirmed EVD cases, following completion of contact tracing. The goal of this HF-based ACF system was to look for undetected EVD cases among patients that visited HFs beginning one week prior to the system’s implementation. Methods From 23 June – 24 July 2018, ACF teams visited HFs in Mbandaka and reviewed all medical records as far back as 17 June for any consultations meeting the suspected EVD case definition. The teams then assessed whether to validate these as suspected EVD cases based on factors such as recovery, epidemiological links, and their clinical judgement. ACF teams also assessed HFs’ awareness of EVD symptoms and the process for alerting suspected cases. We calculated descriptive statistics regarding the characteristics of reviewed consultations, alert cases, and visited HFs. We also used univariate and multivariate random effects logistic regression models to evaluate the impact of repeated ACF visits to the same HF on the staff’s awareness of EVD. Results ACF teams reviewed 37,746 consultations, of which 690 met the definition of a suspected case of EVD. Two were validated as suspected EVD cases and transferred to the Ebola Treatment Unit for testing; both tested negative. Repeated ACF visits to the same HF were significantly associated with improved EVD awareness (p Conclusion HF-based ACF during EVD outbreaks may improve EVD awareness and reveal many individuals meeting the suspected case definition. However, many who meet this definition may not have EVD, depending on the population size covered by ACF and amount of ongoing EVD transmission. Given the burdensome procedure of testing suspected EVD cases, future HF-based ACF systems would benefit from improved clarity on which patients require further testing.

In 2015, favipiravir was administered on a compassionate-use basis to patients with Ebola virus disease in Guinea. This study reveals a trend toward improved survival in favipiravir-treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time., Background In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus–specific reverse transcription–polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis. Methods To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome. Results The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors. Conclusions Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

Summary Background The real-time generation of information about pathogen genomes has become a vital goal for transmission analysis and characterisation in rapid outbreak responses. In response to the recently established genomic capacity in the Democratic Republic of the Congo, we explored the real-time generation of genomic information at the start of the 2018 Ebola virus disease (EVD) outbreak in North Kivu Province. Methods We used targeted-enrichment sequencing to produce two coding-complete Ebola virus genomes 5 days after declaration of the EVD outbreak in North Kivu. Subsequent sequencing efforts yielded an additional 46 genomes. Genomic information was used to assess early transmission, medical countermeasures, and evolution of Ebola virus. Findings The genomic information demonstrated that the EVD outbreak in the North Kivu and Ituri Provinces was distinct from the 2018 EVD outbreak in Equateur Province of the Democratic Republic of the Congo. Primer and probe mismatches to Ebola virus were identified in silico for all deployed diagnostic PCR assays, with the exception of the Cepheid GeneXpert GP assay. Interpretation The first two coding-complete genomes provided actionable information in real-time for the deployment of the rVSVΔG-ZEBOV-GP Ebola virus envelope glycoprotein vaccine, available therapeutics, and sequence-based diagnostic assays. Based on the mutations identified in the Ebola virus surface glycoprotein (GP12) observed in all 48 genomes, deployed monoclonal antibody therapeutics (mAb114 and ZMapp) should be efficacious against the circulating Ebola virus variant. Rapid Ebola virus genomic characterisation should be included in routine EVD outbreak response procedures to ascertain efficacy of medical countermeasures. Funding Defense Biological Product Assurance Office.

In October 2015, a new case of Ebola virus disease in Guinea was detected. Case investigation, serology, and whole-genome sequencing indicated possible transmission of the virus from an Ebola virus disease survivor to another person and then to the case-patient reported here. This transmission chain over 11 months suggests slow Ebola virus evolution.

Objectives The objective of the study was to present the findings of an audit tool aimed at assessing contact tracing activities during an Ebola outbreak. Methods The tool was based on Ebola guidelines and observations in the field. It was composed of 38 indicators covering contact tracing preparatives, resources, procedures and results. Results All contact tracing teams were assessed in Boke and Conakry prefectures (24 supervisors, 22 community workers, 442 contacts) between 1 July and 10 August 2015. Contact lists had less than a 40% accomplishment rate. 7% of the contacts were not seen by community workers or supervisors. 'No touch policy' was fully respected. Conclusion Audit checklist helped to systematically identify critical issues related to contact tracing.

Publisher's version (útgefin grein), [No abstract available], The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Background The PR1MaC study was conducted to evaluate the integration of Chronic Disease Prevention and Management services into primary care practices and was reported effective. The aim of this study was to further explore the effects of the PR1MaC intervention on patients and their family. Methods We conducted a qualitative study embedded in a randomized controlled trial. The trial was implemented in eight primary health care practices in the Saguenay region, Quebec, Canada. The interdisciplinary patient-centred team-based intervention included self-management support and a motivational approach. We conducted focus groups and semi-directed individual interviews with patients, family members and healthcare professionals. Results Perceived positive effects can be grouped into six major themes: awareness, improved knowledge, improved motivation and empowerment, adoption of healthy behaviours, improvement of health status and improvement of quality of life. On the negative side, some participants reported lack of sustainability of newly acquired benefits in the months following the intervention. Conclusions Integrating chronic disease prevention and management services into primary care settings had impacts on patients and their family members. These findings are consistent with findings that were reported in the quantitative study. Further studies should address longterm sustainabilility in terms of benefits for the patients. Trial registration ClinicalTrials.gov, no.: NCT01319656. Electronic supplementary material The online version of this article (10.1186/s12875-018-0898-z) contains supplementary material, which is available to authorized users.

Background Efforts to improve maternal health are increasingly focused on improving the quality of care provided to women at health facilities, including the promotion of respectful care and eliminating mistreatment of women during childbirth. A WHO-led multi-country research project aims to develop and validate two tools (labor observation and community survey) to measure how women are treated during facility-based childbirth. This paper describes the development process for these measurement tools, and how they were implemented in a multi-country study (Ghana, Guinea, Myanmar and Nigeria). Methods An iterative mixed-methods approach was used to develop two measurement tools. Methodological development was conducted in four steps: (1) initial tool development; (2) validity testing, item adjustment and piloting of paper-based tools; (3) conversion to digital, tablet-based tools; and (4) data collection and analysis. These steps included systematic reviews, primary qualitative research, mapping of existing tools, item consolidation, peer review by key stakeholders and piloting. Results The development, structure, administration format, and implementation of the labor observation and community survey tools are described. For the labor observations, a total of 2016 women participated: 408 in Nigeria, 682 in Guinea, and 926 in Ghana. For the community survey, a total of 2672 women participated: 561 in Nigeria, 644 in Guinea, 836 in Ghana, and 631 in Myanmar. Of the 2016 women who participated in the labor observations, 1536 women (76.2%) also participated in the community survey and have linked data: 779 in Ghana, 425 in Guinea, and 332 in Nigeria. Conclusions An important step to improve the quality of maternity care is to understand the magnitude and burden of mistreatment across contexts. Researchers and healthcare providers in maternal health are encouraged to use and implement these tools, to inform the development of more women-centered, respectful maternity healthcare services. By measuring the prevalence of mistreatment of women during childbirth, we will be able to design and implement programs and policies to transform maternity services. Electronic supplementary material The online version of this article (10.1186/s12874-018-0603-x) contains supplementary material, which is available to authorized users.

Background\ud \ud On May 8, 2018, the Government of the Democratic Republic of the Congo reported an outbreak of Ebola virus disease in Équateur Province in the northwest of the country. The remoteness of most affected communities and the involvement of an urban centre connected to the capital city and neighbouring countries makes this outbreak the most complex and high risk ever experienced by the Democratic Republic of the Congo. We provide early epidemiological information arising from the ongoing investigation of this outbreak.\ud Methods\ud \ud We classified cases as suspected, probable, or confirmed using national case definitions of the Democratic Republic of the Congo Ministère de la Santé Publique. We investigated all cases to obtain demographic characteristics, determine possible exposures, describe signs and symptoms, and identify contacts to be followed up for 21 days. We also estimated the reproduction number and projected number of cases for the 4-week period from May 25, to June 21, 2018.\ud Findings\ud \ud As of May 30, 2018, 50 cases (37 confirmed, 13 probable) of Zaire ebolavirus were reported in the Democratic Republic of the Congo. 21 (42%) were reported in Bikoro, 25 (50%) in Iboko, and four (8%) in Wangata health zones. Wangata is part of Mbandaka, the urban capital of Équateur Province, which is connected to major national and international transport routes. By May 30, 2018, 25 deaths from Ebola virus disease had been reported, with a case fatality ratio of 56% (95% CI 39–72) after adjustment for censoring. This case fatality ratio is consistent with estimates for the 2014–16 west African Ebola virus disease epidemic (p=0·427). The median age of people with confirmed or probable infection was 40 years (range 8–80) and 30 (60%) were male. The most commonly reported signs and symptoms in people with confirmed or probable Ebola virus disease were fever (40 [95%] of 42 cases), intense general fatigue (37 [90%] of 41 cases), and loss of appetite (37 [90%] of 41 cases). Gastrointestinal symptoms were frequently reported, and 14 (33%) of 43 people reported haemorrhagic signs. Time from illness onset and hospitalisation to sample testing decreased over time. By May 30, 2018, 1458 contacts had been identified, of which 746 (51%) remained under active follow-up. The estimated reproduction number was 1·03 (95% credible interval 0·83–1·37) and the cumulative case incidence for the outbreak by June 21, 2018, is projected to be 78 confirmed cases (37–281), assuming heterogeneous transmissibility.\ud Interpretation\ud \ud The ongoing Ebola virus outbreak in the Democratic Republic of the Congo has similar epidemiological features to previous Ebola virus disease outbreaks. Early detection, rapid patient isolation, contact tracing, and the ongoing vaccination programme should sufficiently control the outbreak. The forecast of the number of cases does not exceed the current capacity to respond if the epidemiological situation does not change. The information presented, although preliminary, has been essential in guiding the ongoing investigation and response to this outbreak.

On 11 May 2015, the Dubréka prefecture, Guinea, reported nine laboratory-confirmed cases of Ebola virus disease (EVD). None could be epidemiologically linked to cases previously reported in the prefecture. We describe the epidemiological and molecular investigations of this event. We used the Dubréka EVD registers and the Ebola treatment centre’s (ETC) records to characterise chains of transmission. Real-time field Ebola virus sequencing was employed to support epidemiological results. An epidemiological cluster of 32 cases was found, of which 27 were laboratory confirmed, 24 were isolated and 20 died. Real-time viral sequencing on 12 cases demonstrated SL3 lineage viruses with sequences differing by one to three nt inside a single phylogenetic cluster. For isolated cases, the average time between symptom onset and ETC referral was 2.8 days (interquartile range (IQR): 1–4). The average time between sample collection and molecular results’ availability was 3 days (IQR: 2–5). In an area with scarce resources, the genetic characterisation supported the outbreak investigations in real time, linking cases where epidemiological investigation was limited and reassuring that the responsible strain was already circulating in Guinea. We recommend coupling thorough epidemiological and genomic investigations to control EVD clusters.

Background Human Ebola infection is characterized by a paralysis of the immune system. A signature of αβ T cells in fatal Ebola infection has been recently proposed, while the involvement of innate immune cells in the protection/pathogenesis of Ebola infection is unknown. Aim of this study was to analyze γδ T and NK cells in patients from the Ebola outbreak of 2014–2015 occurred in West Africa, and to assess their association with the clinical outcome. Methodology/Principal findings Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Centre in Guinea. Patients were divided in two groups on the basis of the clinical outcome. The analysis was performed by using multiparametric flow cytometry established by the European Mobile Laboratory in the field. A low frequency of Vδ2 T-cells was observed during Ebola infection, independently from the clinical outcome. Moreover, Vδ2 T-cells from Ebola patients massively expressed CD95 apoptotic marker, suggesting the involvement of apoptotic mechanisms in Vδ2 T-cell loss. Interestingly, Vδ2 T-cells from survivors expressed an effector phenotype and presented a lower expression of the CTLA-4 exhaustion marker than fatalities, suggesting a role of effector Vδ2 T-cells in the protection. Furthermore, patients with fatal Ebola infection were characterized by a lower NK cell frequency than patients with non fatal infection. In particular, both CD56bright and CD56dim NK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56neg NK cells was associated to non-fatal infections. Finally, NK activation and expression of NKp46 and CD158a were independent from clinical outcome. Conclusions/Significances Altogether, the data suggest that both effector Vδ2 T-cells and NK cells may play a role in the complex network of protective response to EBOV infection. Further studies are required to characterize the protective effector functions of Vδ2 and NK cells., Author summary Human Ebola infection presents a high lethality rate and is characterized by a paralysis of the immune response. The definition of the protective immune profile during Ebola infection represents a main challenge useful in vaccine and therapy design. In particular, the protective/pathogenetic involvement of innate immune cells during Ebola infection in humans remains to be clarified. Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Center in Guinea, and the profiling of innate immunity was correlated with the clinical outcome. Our results show that both effector Vδ2 T-cells and NK cells were associated with survival, suggesting their involvement in the complex network of protective response to EBOV infection.

The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics. ispartof: Nature vol:544 issue:7650 pages:309- ispartof: location:England status: published

Background The history of African indigenous cattle and their adaptation to environmental and human selection pressure is at the root of their remarkable diversity. Characterization of this diversity is an essential step towards understanding the genomic basis of productivity and adaptation to survival under African farming systems. Results We analyze patterns of African cattle genetic variation by sequencing 48 genomes from five indigenous populations and comparing them to the genomes of 53 commercial taurine breeds. We find the highest genetic diversity among African zebu and sanga cattle. Our search for genomic regions under selection reveals signatures of selection for environmental adaptive traits. In particular, we identify signatures of selection including genes and/or pathways controlling anemia and feeding behavior in the trypanotolerant N’Dama, coat color and horn development in Ankole, and heat tolerance and tick resistance across African cattle especially in zebu breeds. Conclusions Our findings unravel at the genome-wide level, the unique adaptive diversity of African cattle while emphasizing the opportunities for sustainable improvement of livestock productivity on the continent. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1153-y) contains supplementary material, which is available to authorized users.

BACKGROUND\ud \ud On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern."\ud \ud METHODS\ud \ud By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa - Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14.\ud \ud RESULTS\ud \ud The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R-0) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total.\ud \ud CONCLUSIONS\ud \ud These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months.

Background The international impact, rapid widespread transmission, and reporting delays during the 2014 Ebola outbreak in West Africa highlighted the need for a global, centralized database to inform outbreak response. The World Health Organization and Emerging and Dangerous Pathogens Laboratory Network addressed this need by supporting the development of a global laboratory database. Methods Specimens were collected in the affected countries from patients and dead bodies meeting the case definitions for Ebola virus disease. Test results were entered in nationally standardized spreadsheets and consolidated onto a central server. Results From March 2014 through August 2016, 256343 specimens tested for Ebola virus disease were captured in the database. Thirty-one specimen types were collected, and a variety of diagnostic tests were performed. Regular analysis of data described the functionality of laboratory and response systems, positivity rates, and the geographic distribution of specimens. Conclusion With data standardization and end user buy-in, the collection and analysis of large amounts of data with multiple stakeholders and collaborators across various user-access levels was made possible and contributed to outbreak response needs. The usefulness and value of a multifunctional global laboratory database is far reaching, with uses including virtual biobanking, disease forecasting, and adaption to other disease outbreaks.

Background Reducing maternal morbidity and mortality remains a key health challenge in Guinea. Anecdotal evidence suggests that women in Guinea are subjected to mistreatment during childbirth in health facilities, but limited research exists on this topic. This study was conducted to better understand the social norms and the acceptability of four scenarios of mistreatment during childbirth, from the perspectives of women and service providers. Methods This study used qualitative methods including in-depth interviews (IDIs) and focus group discussions (FGDs) with women of reproductive age, midwives, nurses and doctors. This study was conducted in one urban area (Mamou) and one peri-urban area (Pita) in Guinea. Participants were presented with four scenarios of mistreatment during childbirth, including a provider: (1) slapping a woman; (2) verbally abusing a woman; (3) refusing to help a woman; and (4) forcing a woman to give birth on the floor. Data were collected in local languages (Pular and Malinké) and French, and transcribed and analyzed in French. We used a thematic analysis approach and manually coded the data using a codebook developed for the project. Results A total of 40 IDIs and eight FGDs were conducted with women of reproductive age, 5 IDIs with doctors, and 13 IDIs with midwives. Most women were not accepting of any of the scenarios, unless the action was perceived to be used to save the life of the mother or child. However, they perceived a woman’s disobedience and uncooperativeness to contribute to her poor treatment. Women reacted to this mistreatment by accepting poor treatment, refusal to use the same hospital, revenge against the provider or complaints to hospital management. Service providers were accepting of mistreatment when women were disobedient, uncooperative, or to save the life of the baby. Conclusions This is the first known study on mistreatment of women during childbirth to be conducted in Guinea. Both women and service providers were accepting of mistreatment during childbirth under certain conditions. Any approach to preventing and eliminating mistreatment during childbirth must consider these important contextual and social norms and develop a comprehensive intervention that addresses root causes. Further research is needed on how to measure mistreatment during childbirth in Guinea.

La plaie carotidienne lors du cathétérisme jugulaire veineux est un accident rare mais pouvant être dramatique. Nous rapportons un cas d'hématome cervical compressif avec hémothorax survenu à la suite d'une plaie de l'artère carotide commune au décours d'un cathétérisme veineux jugulaire interne. Le diagnostic et la prise en charge de ce type de complication sont discutés.

We report on an Ebola virus disease (EVD) survivor who showed Ebola virus (EBOV) in seminal fluid 531 days after onset of disease. The persisting virus was sexually transmitted in February 2016, about 470 days after onset of symptoms, and caused a new cluster of EVD in Guinea and Liberia.

Background The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. Methods and Findings Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). Conclusions Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population., In this retrospective observational study, Christophe Fraser and colleagues analyze the exposure patterns associated with Ebola transmission during the 2013-2016 epidemic in West Africa., Author Summary Why Was This Study Done? Knowing how and from whom individuals acquire infection can help inform the response to limit the impact of an epidemic; this study presents updated versions of analyses initially performed to assist the international response during the 2013–2016 Ebola epidemic in West Africa. Over 19,000 individuals with confirmed or probable Ebola (“cases”) were reported in West Africa by 4 May 2015. Cases were asked whether they had exposure to potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. What Did the Researchers Do and Find? We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. Non-funeral exposures were strongly peaked around the time of death of the contact. There was evidence of super-spreading, with only 20% of cases accounting for at least 73% of new infections. What Do These Findings Mean? Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. The data are highly detailed despite the challenging circumstances in the three countries; however, the analyses were limited by data quality, mostly missing data and incorrect entries. In light of viral persistence in reservoirs, it is vital to maintain active surveillance and analysis of Ebola outbreaks to avoid and contain future outbreaks.

Summary Background During the 2014–2015 Ebola Virus Disease (EVD) outbreak in N'Zerekore, Forested Guinea, modes of transmission remained unexamined for a number of new cases. We used network visualization to investigate EVD transmission chains (TC) in seven sub-prefectures of N'Zerekore in order to adapt outbreak response. Methods Between August 2014 and February 2015, the EVD outbreak response team including the World Health Organization (WHO) and local health authorities routinely collected information among new cases regarding hospital visits, cases within a household, participation in burials, as well as dates of symptom onset, serial intervals (SI) and exposure to EVD. SI's were defined as the interval between symptom onset in an index case and symptom onset in a secondary case infected by that index case. Cases who reported hospital visits, contact with a case in the household or participating in burials were attributed to these exposures. Results We identified seven TC (two urban and five rural) gathering characteristics of 109 probable/confirmed cases. Overall, 61% (66 cases, SI range: 7–20 days) were household related, 32% (35 cases, SI range 8–30 days) were household or burial related and 7% (8 cases, SI range: 4–20 days) were hospital-related. In the urban chains (18 cases, SI range: 7–20 days), 12 cases were household related and 6 cases were hospital related, none where household or burial related. In the rural chains (84 cases, SI range: 7–30 days), 60% (50 cases) were household related, 1% (1 case) was hospital related and 39% (34 cases) were household or burial related. No cases reported multiple exposures. Conclusions Network visualization during field response is crucial in enhancing local control strategies, refining outbreak response and aiding rapid response teams in insuring psychosocial and socio-economic recovery. Urban settings need to focus on reducing hospital EVD transmission whereas rural settings should focus on raising awareness of transmission within a household and safeguarding EVD burials.

BACKGROUND During the Ebola outbreak in Guinea, community resistance obstructed case investigation and response. We investigated a cluster of Ebola cases that were hiding in the forest, refusing external help, to identify sociocultural determinants related to community resistance. METHODS Participant observation, interviews and focus group discussions were carried out. RESULTS Most villagers feared the Ebola treatment centre (ETC) as there was the belief that people were killed in ETCs for organ trade. Four survivors accompanied back to the village from the ETC shared their experiences and reassured their neighbours. Subsequently, community compliance with contact tracing improved, leading to the timely detection of cases. CONCLUSIONS Engaging Ebola virus disease survivors improved community compliance. Understanding the sociocultural context and community perceptions may improve community engagement and prevent Ebola virus transmission.

Background The case fatality ratio (CFR) of Ebola virus disease (EVD) can vary over time and space for reasons that are not fully understood. This makes it difficult to define the baseline CFRs needed to evaluate treatments in the absence of randomized controls. Here, we investigate whether viremia in EVD patients may be used to evaluate baseline EVD CFRs. Methods and Findings We analyzed the laboratory and epidemiological records of patients with EVD confirmed by reverse transcription PCR hospitalized in the Conakry area, Guinea, between 1 March 2014 and 28 February 2015. We used viremia and other variables to model the CFR. Data for 699 EVD patients were analyzed. In the week following symptom onset, mean viremia remained stable, and the CFR increased with viremia, V, from 21% (95% CI 16%–27%) for low viremia (V < 104.4 copies/ml) to 53% (95% CI 44%–61%) for intermediate viremia (104.4 ≤ V < 105.2 copies/ml) and 81% (95% CI 75%–87%) for high viremia (V ≥ 105.2 copies/ml). Compared to adults (15–44 y old [y.o.]), the CFR was larger in young children (0–4 y.o.) (odds ratio [OR]: 2.44; 95% CI 1.02–5.86) and older adults (≥45 y.o.) (OR: 2.84; 95% CI 1.81–4.46) but lower in children (5–14 y.o.) (OR: 0.46; 95% CI 0.24–0.86). An order of magnitude increase in mean viremia in cases after July 2014 compared to those before coincided with a 14% increase in the CFR. Our findings come from a large hospital-based study in Conakry and may not be generalizable to settings with different case profiles, such as with individuals who never sought care. Conclusions Viremia in EVD patients was a strong predictor of death that partly explained variations in CFR in the study population. This study provides baseline CFRs by viremia group, which allow appropriate adjustment when estimating efficacy in treatment studies. In randomized controlled trials, stratifying analysis on viremia groups could reduce sample size requirements by 25%. We hypothesize that monitoring the viremia of hospitalized patients may inform the ability of surveillance systems to detect EVD patients from the different severity strata., In a retrospective cohort study, Simon Cauchemez and colleagues find viral load can predict case fatality ratios among patients with Ebola Virus., Editors' Summary Background During the current outbreak of Ebola virus disease (EVD) in West Africa, which started in December 2013, there have been more than 28,000 confirmed, probable, and suspected cases of EVD and more than 11,000 deaths from the disease. Ebola virus is transmitted to people from wild animals and spreads in human populations through direct contact with the bodily fluids (including blood, saliva, and urine) or organs of infected people or through contact with bedding and other materials contaminated with bodily fluids. The symptoms of EVD, which start 2–21 days after infection, include fever, headache, vomiting, diarrhea, and internal and external bleeding. Infected individuals are not infectious until they develop symptoms but remain infectious as long as their bodily fluids contain virus. There is no proven treatment or vaccine for EVD, although several treatments are now being assessed in people following promising laboratory studies. Supportive care—given under strict isolation conditions to prevent the spread of the disease to other patients or to healthcare workers—improves survival. Why Was This Study Done? Ideally, the efficacy of a potential treatment for any disease is assessed in a randomized controlled trial, a study that compares outcomes among people chosen at random to receive the treatment with outcomes among people given a placebo (dummy treatment). However, because EVD is frequently fatal, randomized controlled trials of potential treatments are considered unethical. Instead, studies evaluating treatments for EVD usually compare the case fatality ratio (CFR; the number of deaths caused by a disease divided by the number of cases of that disease; a CFR of 100% indicates that everyone who develops the disease dies) among treated patients with a baseline CFR estimated from historical data. But the CFR of EVD varies markedly over time and space for poorly understood reasons (for example, changes in patient care or variations in the detection of people with disease of different severity might change the CFR). Thus, the CFR in the treatment group could differ from the baseline CFR for reasons that are independent of the treatment. To find a way around this problem, in this retrospective cohort study, the researchers investigate whether there is a relationship between viremia (the amount of virus in the blood) and the CFR among patients with EVD. What Did the Researchers Do and Find? The researchers used laboratory and epidemiological data (for example, patient age and date of symptom onset and death; epidemiology is the study of disease patterns in populations) to investigate the relationship between viremia and CFR among 699 patients with confirmed EVD hospitalized in the Conakry area of Guinea between March 2014 and February 2015. In the week following symptom onset, mean (average) viremia remained stable, and the CFR among the patients increased with the level of viremia. Thus, the CFRs for patients with low, intermediate, and high viremia (defined by the number of virus copies per milliliter of blood) were 21%, 53%, and 81%, respectively. Compared to adults aged 15–44 years, young children (aged less than five years) and older adults had a higher CFR, but children aged 5–14 years had a lower CFR. Notably, the CFR in the study population was 14% higher after July 2014 than in the months of March–July 2014, an increase that coincided with a ten-fold increase in the average level of viremia in the population. What Do These Findings Mean? These findings suggest that viremia is a strong predictor of death that can partly explain variations in the CFR of EVD. Because these findings are based on data collected from hospitalized patients, they may not be generalizable to other settings. Importantly, however, these findings provide estimates of CFR by viremia group that can now be used to adjust risk when undertaking clinical evaluations of EVD-specific treatments. That is, by allowing for differing levels of viremia, it will be possible to assess the efficacy of treatments for EVD more accurately in nonrandomized clinical trials. Moreover, the researchers calculate that stratification of patients by viremia group could reduce the sample size needed in any randomized trials that are undertaken (for example, comparisons of two potential treatments) by 25%. Finally, the researchers suggest that monitoring viremia among patients hospitalized for EVD might provide information about the ability of different surveillance systems to detect patients with different levels of disease severity (probability of death). Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001908. The World Health Organization (WHO) provides information about EVD, information about potential EVD therapies, and regular updates on the current EVD epidemic; a summary of the discussion of a WHO Ethics Working Group Meeting on the ethical issues related trials of EVD treatments is available; the WHO website also provides information about efforts to control Ebola in the field and personal stories from people who have survived EVD The UK National Health Service Choices website provides detailed information on EVD The US Centers for Disease Control and Prevention also provides information about http://www.cdc.gov/vhf/ebola/EVD

A nanopore DNA sequencer is used for real-time genomic surveillance of the Ebola virus epidemic in the field in Guinea; the authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection. This paper reports the use of nanopore DNA sequencers (known as MinIONs) for real-time genomic surveillance of the Ebola virus epidemic, in the field in Guinea. The authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection. The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths1. Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 × 10−3 and 1.42 × 10−3 mutations per site per year. This is equivalent to 16–27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic2,3,4,5,6,7. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions8. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities9. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15–60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.

West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak. ispartof: Nature vol:524 issue:7563 pages:97-101 ispartof: location:England status: published

Background Every woman has the right to dignified, respectful care during childbirth. Recent evidence has demonstrated that globally many women experience mistreatment during labour and childbirth in health facilities, which can pose a significant barrier to women attending facilities for delivery and can contribute to poor birth experiences and adverse outcomes for women and newborns. However there is no clear consensus on how mistreatment of women during childbirth in facilities is defined and measured. We propose using a two-phased, mixed-methods study design in four countries to address these research gaps. This protocol describes the Phase 1 qualitative research activities. Methods/Design We will employ qualitative research methodologies among women, healthcare providers and administrators in the facility catchment areas of two health facilities in each country: Ghana, Guinea, Myanmar and Nigeria. In-depth interviews (IDIs) and focus group discussions (FGDs) will be conducted among women of reproductive age (15–49 years) to explore their perceptions and experiences of facility-based childbirth care, focused on how they were treated by healthcare workers and perceived factors affecting how they were treated. IDIs will also be conducted with healthcare providers of different cadres (e.g.: nurses, midwives, medical officers, specialist obstetricians) and facility administrators working in the selected facilities to explore healthcare providers’ perceptions and experiences of facility-based childbirth care and how staff are treated, colleagues and supervisors. Audio recordings will be transcribed and translated to English. Textual data will be analysed using a thematic framework approach and will consist of two levels of analysis: (1) conduct of local analysis workshops with the research assistants in each country; and (2) line-by-line coding to develop a thematic framework and coding scheme. Discussion This study serves several roles. It will provide an in-depth understanding of how women are treated during childbirth in four countries and perceived factors associated with this mistreatment. It will also provide data on where and how an intervention could be developed to reduce mistreatment and promote respectful care. The findings from this study will contribute to the development of tools to measure the prevalence of mistreatment of women during facility-based childbirth.

A hospital outbreak of CCHF in Mauritania alerted authorities to sporadic cases occurring in the community; in all, 38 persons were infected., From February to August 2003, 38 persons were infected with Crimean-Congo hemorrhagic fever (CCHF) virus in Mauritania; 35 of these persons were residents of Nouakchott. The first patient was a young woman who became ill shortly after butchering a goat. She transmitted the infection to 15 persons in the hospital where she was admitted and four members of her family. In Nouakchott, two disease clusters and 11 isolated cases were identified. The case-fatality ratio was 28.6%. Of the patients not infected by the first case-patient, almost half were butchers, which suggests that the primary mode of animal-to-human transmission was direct contact with blood of infected animals. The hospital outbreak alerted health authorities to sporadic cases that occurred in the following weeks, which would have probably gone otherwise unnoticed. Studies must be conducted to determine the potential risk for continued sporadic outbreaks of CCHF in humans and to propose prevention measures.

A 9-month-old infant died from Ebola virus (EBOV) disease with unknown epidemiological link. While her parents did not report previous illness, laboratory investigations revealed persisting EBOV RNA in the mother’s breast milk and the father’s seminal fluid. Genomic analysis strongly suggests EBOV transmission to the child through breastfeeding.

Phylogenetic studies demonstrated that outbreak strains belonged to the East-Central African lineage., In October 2003, 9 human cases of hemorrhagic fever were reported in 3 provinces of Mauritania, West Africa. Test results showed acute Rift Valley fever virus (RVFV) infection, and a field investigation found recent circulation of RVFV with a prevalence rate of 25.5% (25/98) and 4 deaths among the 25 laboratory-confirmed case-patients. Immunoglobulin M against RVFV was found in 46% (25/54) of domestic animals. RVFV was also isolated from the mosquito species Culex poicilipes. Genetic comparison of virion segments indicated little variation among the strains isolated. However, phylogenetic studies clearly demonstrated that these strains belonged to the East-Central African lineage for all segments. To our knowledge, this is the first time viruses of this lineage have been observed in an outbreak in West Africa. Whether these strains were introduced or are endemic in West Africa remains to be determined.

Doping in sports is as old as sports, but it grew considerably during the 20th century with the arrival in stadiums during the 1990s of amphetamines and anabolic steroids as well as such peptide hormones as erythropoietin. The international fight against doping took a giant step forward in 1999 with the creation of the world antidoping agency (WADA). This study is part of that fight. It follows an earlier survey of retail pharmacists in Senegal and aims to evaluate the knowledge about doping of doctors belonging to the Senegalese Association of Sports Medicine and to assess their attitude towards this phenomenon. Its goal is to determine how best to involve them in preventive actions. We conducted a survey in 2001 and randomly selected and interviewed 60 of the 92 doctors in the association. The questionnaire focused on three areas: their knowledge of doping, their attitudes to it, and the means of prevention that they proposed. The results showed that only 11 of the 60 doctors knew the definition of doping and 15% of doctors could not cite any family of doping products. They were aware mainly of testosterone and other anabolic steroids (84.3%), then amphetamines and other stimulants (64.7%), and finally peptide hormones (58.8%). The subjects mentioned blood doping and pharmacological manipulations as forbidden methods. They considered that the four groups of drugs most often used by athletes for doping were, in descending order, anabolic steroids, stimulants, peptide hormones and corticoids. Eighty per cent of doctors think that Senegalese athletes use doping products and that the sports most involved are football, wrestling, track and field and basketball. They also think that doping is a form of drug addiction and a public health problem. Eleven doctors (18%) said they had been contacted for information on use of doping products. The interviewees consider that the three best methods of prevention include information about side effects, unannounced urine and blood tests, and sanctions. This work shows that Senegalese athletes may use doping; it contains no direct proofs but many indirect indicators. Success against doping requires preventive activities that should be conducted jointly for trainers, sports federations and doctors of the Senegalese Association of Sports Medicine and then by all of them for athletes, who are the primary targets of any prevention campaign.

Oro-facial noma is an oral gangrene occurring in early childhood in extremely poor areas. As many as 70-90% of those with noma die, and to date, there is no satisfactory treatment to fight this disease. Within the context of the World Health Organization international program against noma, a 13-year retrospective study based on clinical records was carried out in Dakar, Senegal in an attempt to understand the epidemiology of noma. Between 1981 and 1993, 199 cases of noma were identified, among them; 36.7% were acute cases and 63.3% showed sequelae. Chronic sequelae of noma were seen in patients 2-41 years of age, but the acute phase of noma was found only in young children (77.7% in those 1-4 years of age, maximum age = 9 years, mean age +/- SD age = 3.4 +/- 1.9 years). A total of 73.1% of the cases with acute disease were reported in the Dakar, Diourbel and Kaolack regions during the dry season (57.0% of the cases). The lesions of progressive noma were localized mainly on the upper lip (42.4%) and the cheek (31.1%). A total of 96.9% of the patients with acute diseases were had poor general health with serious associated diseases; only 20.0% had a good vital prognosis. The development of epidemiologic surveillance programs for noma should be a public health priority in Senegal.